One of 8 American women will develop breast cancer. Recent studies indicate that Her-2/neu (ERBB2) may be one of the genes responsible for the transformation of normal breast epithelial cells to a cancerous phenotype. This proposal is focused on the purification and characterization of a nuclear matrix protein that may function as a molecular switch responsible for the regulation of the ERBB2 gene in the development and progression of breast cancer. A nuclear matrix protein has been identified that is found at high concentration in breast cancer tissues, but which is not present at appreciable levels in normal or benign breast tissues. This protein specifically interacts with a unique promoter region of the ERBB2 gene and appears to be accumulated in the nuclear matrix compartment. The hypothesis is that the level of this putative transcription factor regulates expression of the ERBB2 gene and concomitant loss of growth control. Therefore, the proposal is to isolate, purify, and characterize ERP-NM and to develop antibodies specific for it. In subsequent Phase II experiments, the plan is to clone the gene encoding ERP-NM, make cDNA probes for it, and determine the level and distribution of ERP-NM in various stages of human breast cancer.
